Department of Pathology and Lab Medicine, Emory University School of Medicine, Atlanta, GA, USA.
Imagerie Moléculaire et Stratégies Théranostiques, Centre de Lutte Contre le Cancer Jean Perrin, Université Clermont Auvergne, Clermont Ferrand, France.
J Natl Cancer Inst. 2022 May 9;114(5):664-675. doi: 10.1093/jnci/djab121.
Triple-negative breast cancer (TNBC) accounts for approximately 12% to 17% of all breast cancers and has an aggressive clinical behavior. Increased tumor-infiltrating lymphocyte counts are prognostic for survival in TNBC, making this disease a potential target for cancer immunotherapy. Research on immunophenotyping of tumor-infiltrating lymphocytes is revealing molecular and structural organization in the tumor microenvironment that may predict patient prognosis. The anti-programmed death-ligand 1 (PD-L1) antibody atezolizumab plus nab-paclitaxel was the first cancer immunotherapy combination to demonstrate progression-free survival benefit and clinically meaningful overall survival benefit in the first-line treatment of metastatic TNBC (mTNBC) in patients with PD-L1-expressing tumor-infiltrating immune cells in 1% or more of the tumor area. This led to its United States and European Union approval for mTNBC and US approval of the VENTANA PD-L1 (SP142) assay as a companion diagnostic immunohistochemistry assay. Subsequently, the anti-programmed death-1 (PD-1 ) antibody pembrolizumab plus chemotherapy was approved by the US Food and Drug Administration for mTNBC based on progression-free survival benefit in patients with a combined positive score of at least 10 by its concurrently approved 22C3 companion diagnostic assay. Treatment guidelines now recommend PD-L1 testing for patients with mTNBC, and the testing landscape will likely become increasingly complex as new anti-PD-L1 and anti-PD-1 agents and diagnostics are approved for TNBC. Integrating PD-L1 testing into current diagnostic workflows for mTNBC may provide more treatment options for these patients. Therefore, it is critical for medical oncologists and pathologists to understand the available assays and their relevance to therapeutic options to develop an appropriate workflow for immunohistochemistry testing.
三阴性乳腺癌（TNBC）约占所有乳腺癌的 12%至 17%，具有侵袭性的临床行为。肿瘤浸润淋巴细胞计数的增加与 TNBC 的生存预后相关，使这种疾病成为癌症免疫治疗的潜在靶点。对肿瘤浸润淋巴细胞免疫表型的研究揭示了肿瘤微环境中的分子和结构组织，这些可能预测患者的预后。抗程序性死亡配体 1（PD-L1）抗体阿特珠单抗联合 nab-紫杉醇是第一种癌症免疫治疗联合用药，在肿瘤浸润免疫细胞中 PD-L1 表达 1%或以上的转移性 TNBC（mTNBC）患者的一线治疗中，显示出无进展生存期获益和具有临床意义的总生存期获益。这促使其在美国和欧盟批准用于 mTNBC，以及在美国批准 VENTANA PD-L1（SP142）检测作为伴随诊断免疫组化检测。随后，抗程序性死亡受体 1（PD-1）抗体帕博利珠单抗联合化疗在美国获得批准，用于 mTNBC，基于其同时批准的 22C3 伴随诊断检测的联合阳性评分至少为 10 的患者的无进展生存期获益。治疗指南现在建议对 mTNBC 患者进行 PD-L1 检测，随着新的抗 PD-L1 和抗 PD-1 药物和诊断方法被批准用于 TNBC，检测格局可能变得越来越复杂。将 PD-L1 检测纳入 mTNBC 的当前诊断工作流程可能为这些患者提供更多的治疗选择。因此，肿瘤内科医生和病理学家了解可用的检测方法及其与治疗选择的相关性，以制定适当的免疫组化检测工作流程至关重要。
